Compositions and methods involving direct write optical lithography

ABSTRACT

An improved optical photolithography system and method provides predetermined light patterns generated by a direct write system without the use of photomasks. The Direct Write System provides predetermined light patterns projected on the surface of a substrate (e.g., a wafer) by using a computer controlled means for dynamically generating the predetermined light pattern, e.g., a spatial light modulator. Image patterns are stored in a computer and through electronic control of the spatial light modulator directly illuminate the wafer to define a portion of the polymer array, rather than being defined by a pattern on a photomask. Thus, in the Direct Write System each pixel is illuminated with an optical beam of suitable intensity and the imaging (printing) of an individual feature is determined by computer control of the spatial light modulator at each photolithographic step without the use of a photomask. The Direct Write System including a spatial light modulator is particularly useful in the synthesis of DNA arrays and provides an efficient means for polymer array synthesis by using spatial light modulators to generate a predetermined light pattern that defines the image patterns of a polymer array to be deprotected.

This application relates to provisional application Ser. No. 60/087,333filed May 29, 1998 which is hereby incorporated by reference in itsentirety.

BACKGROUND OF THE INVENTION

1. Technical Field of the Invention

This invention relates to optical lithography and more particularly todirect write optical lithography.

2. Description of the Related Art

Polymer arrays, such as the GeneChip® probe array (Affymetrix, Inc.,Santa Clara, Calif.), can be synthesized using light-directed methodsdescribed, for example, in U.S. Pat. No. Nos. 5,143,854; 5,424,186;5,510,270; 5, 800,992; 5,445,934; 5,744,305; 5,384, 261 and 5,677,195and PCT published application no. WO 95/11995, which are herebyincorporated by reference in their entireties. As an example,light-directed synthesis of oligonucleotides employs 5′-protectednucleosidephosphoramidite “building blocks.” The 5′-protecting groupsmay be either photolabile or acid-labile. A plurality of polymersequences in predefined regions are synthesized by repeated cycles ofdeprotection (selective removal of the protective group) and coupling.Coupling (i.e., nucleotide or monomer addition) occurs only at sitesthat have been deprotected. Three methods of light-directed synthesisare: use of photolabile protecting groups and direct photodeprotection(DPD); use of acid-labile 4,4′-dimethoxytrityl (DMT) protecting groupsand a photoresist; use of DMT protecting groups and a polymer film thatcontains a photoacid generator (PAG).

These methods have many process steps similar to those used insemiconductor integrated circuit manufacturing. These methods also ofteninvolve the use of photomasks (masks) that have a predefined imagepattern which permits the light used for synthesis of the polymer arraysto reach certain regions of a substrate but not others. The substratecan be non-porous, rigid, semi-rigid, etc. It can be formed into a well,a trench, a flat surface, etc. The substrate can include solids, such assiliceous substances such as silicon, glass, fused silica, quart andother solids such as plastics and polymers, such as polyacrylamide,polystyrene, polycarbonate, etc. Typically, the solid substrate iscalled a wafer from which individual chips are made (See the U.S.patents above which are incorporated herein by reference). As such, thepattern formed on the mask is projected onto the wafer to define whichportions of the wafer are to be deprotected and which regions remainprotected. See, for example, U.S. Pat. Nos. 5,593,839 and 5,571,639which are hereby incorporated by reference in their entireties.

The lithographic or photochemical steps in the synthesis of nucleic acidarrays may be performed by contact printing or proximity printing usingphotomasks. For example, an emulsion or chrome-on-glass mask is placedin contact with the wafer, or nearly in contact with the wafer, and thewafer is illuminated through the mask by light having an appropriatewavelength. However, masks can be costly to make and use and are capableof being damaged or lost.

In many cases a different mask having a particular predetermined imagepattern is used for each separate photomasking step, and synthesis of awafer containing many chips requires a plurality of photomasking stepswith different image patterns. For example, synthesis of an array of20mers typically requires approximately seventy photolithographic stepsand related unique photomasks So, using present photolithographicsystems and methods, a plurality of different image pattern masks mustbe pre-generated and changed in the photolithographic system at eachphotomasking step. This plurality of different pattern masks adds leadtime to the process and complexity and inefficiency to thephotolithographic system and method. Further, contact printing using amask can cause defects on the wafer so that some of the reaction sitesare rendered defective. Thus, a photolithographic system and method thatdoes not require such masks and obviates such difficulties would begenerally useful in providing a more efficient and simplifiedlithographic process.

SUMMARY OF THE INVENTION

In view of the above, one advantage of the invention is providing animproved and simplified system and method for optical lithography.

Another advantage of the present invention is providing an opticallithography system and method that dynamically generates an image usinga computer and reconfigurable light modulator.

A further advantage of the present invention is providing an opticallithography system and method that does not use photomasks.

A still further advantage of the present invention is providing anoptical lithography system and method that uses computer generatedelectronic control signals and a spatial light modulator, without anyphotomask, to project a predetermined light pattern onto a surface of asubstrate for the purposes of deprotecting various areas of a polymerarray.

According to one aspect of the invention, polymer array synthesis isperformed using a system without photomasks.

According to a second aspect of the invention, polymer array synthesisis performed using a system with a transmissive spatial light modulatorand without a lens and photomask.

According to another aspect of the invention, a Direct Write Systemtransmits image patterns to be formed on the surface of a substrate(e.g., a wafer). The image patterns are stored in a computer. The DirectWrite System projects light patterns generated from the image patternsonto a surface of the substrate for light-directed polymer synthesis(e.g., oligonucleotide). The light patterns are generated by a spatiallight modulator controlled by a computer, rather than being defined by apattern on a photomask. Thus, in the Direct Write System each pixel isilluminated with an optical beam of suitable intensity and the imaging(printing) of an individual feature on a substrate is determineddynamically by computer control.

According to a further aspect of the invention, polymer array synthesisis accomplished using a class of devices known as spatial lightmodulators to define the image pattern of the polymer array to bedeprotected.

An even further aspect of the present invention provides methods Forsynthesizing polymer arrays using spatial light modulators and thepolymer arrays synthesized using the methods taught herein.

As can be appreciated by one skilled in the art, the invention isrelevant to optical lithography in general, and more specifically tooptical lithography for polymer array synthesis using photolithograpicprocesses. However, it is inherent that the invention is generallyapplicable to eliminating the need for a photomask in opticallithography.

BRIEF DESCRIPTION OF THE DRAWINGS

The above objects, features, and advantages of the present inventionwill become more apparent from the following detailed description takenwith the accompanying drawings in which:

FIG. 1 shows a first embodiment of the invention having a light source,a reflective spatial light modulator, such as a micro-mirror array, anda lens.

FIG. 2 is a diagrammatic representation of a second embodiment of theinvention employing an array of, for example, micro-lenses.

FIG. 3 illustrates a micro-lens array in the form of Fresnel ZonePlates, which may be used in the invention.

FIG. 4 shows a third embodiment of the invention having a transmissivespatial light modulator.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention refers to articles and patents that contain usefulsupplementary information. These references are hereby incorporated byreference in their entireties.

The presently preferred invention is based on the principle that aDirect Write Optical Lithography System will significantly improve thecost, quality, and efficiency of polymer array synthesis by providing amaskless optical lithography system and method where predetermined imagepatterns can be dynamically changed during photolithographic processing.As such, an optical lithography system is provided to include a meansfor dynamically changing an intended image pattern without using aphotomask. One such means includes a spatial light modulator that iselectronically controlled by a computer to generate unique predeterminedimage patterns at each photolithograpic step in polymer array synthesis.The spatial light modulators can be, for example, micromachinedmechanical modulators or microelectronic devices (e.g. liquid crystaldisplay (LCD)). The Direct Write System of the present invention usingsuch spatial light modulators is particularly useful in the synthesis ofpolymer arrays, such as polypeptide, carbohydrate, and nucleic acidarrays. Nucleic acid arrays typically include polynucleotides oroligonucleotides attached to glass, for example, Deoxyribonucleic Acid(DNA) arrays.

Certain preferred embodiments of the invention involve use of themicromachined mechanical modulators to direct the light to predeterminedregions (i.e., known areas on a substrate predefined prior tophotolithography processing) of the substrate on which the of polymersare being synthesized. The predetermined regions of the substrateassociated with, for example, one segment (referred to herein as apixel) of a micromachined mechanical modulator (e.g., a micro-mirrorarray) are referred to herein as features. In each predetermined regionor feature a particular oligonucleotide sequence, for example, issynthesized. The mechanical modulators come in a variety of types, twoof which will be discussed in some detail below.

One type of mechanical modulator is a micro-mirror array which usessmall metal mirrors to selectively reflect a light beam to particularindividual features; thus causing the individual features to selectivelyreceive light from a light source (i.e., turning light on and off of theindividual features). An example is the programmable micro-mirror arrayDigital Micromirror Device (DMD™) manufactured by Texas Instruments,Inc., Dallas, Tex., USA. Texas Instruments markets the arrays primarilyfor projection display applications (e.g., big-screen video) in which ahighly magnified image of the array is projected onto a wall or screen.The present invention shows, however, that with appropriate optics andan appropriate light source, a programmable micro-mirror array can beused for photolithographic synthesis, and in particular for polymerarray synthesis.

The Texas Instruments DMD™ array consists of 640×480 mirrors (the VGAversion) or 800×600 mirrors (the super VGA (SVGA) version). Devices withmore mirrors are under development. Each mirror is 16 μm×16 μm and thereare 1-μm gaps between mirrors. The array is designed to be illuminated20 degrees off axis. Each mirror can be turned on (tilted 10 degrees inone direction) or off (tilted 10 degrees in the other direction). A lens(on axis) images the array onto a target. When a micro-mirror is turnedon, light reflected by the micro-mirror passes through the lens and theimage of the micro-mirror appears bright. When a micro-mirror is turnedoff, light reflected by the micro-mirror misses the lens and the imageof the micro-mirror appears dark. The array can be reconfigured bysoftware (i.e., every micro-mirror in the array can be turned on or offas desired) in a fraction of a second.

An optical lithography system including a micro-mirror array 1 basedspatial light modulator according to one embodiment of the invention isshown in FIG. 1. This embodiment includes a spatial light modulator madeof a micro-mirror array 1, and arc lamp 3, and a lens 2 to project apredetermined image pattern on a chip or wafer (containing many chips)4. In operation, collimated, filtered and homogenized light 5 from thearc lamp 3 is selectively reflected as a light beam 6 according todynamically turned on micro mirrors in the micro-mirror array 1 andtransmitted through lens 2 on to chip or wafer 4 as reflected light beam8. Reflected light from micro-mirrors that are turned off 7 is reflectedin a direction away from the lens 2 so that these areas appear dark tothe lens 2 and chip or wafer 4. Thus, the spatial light modulator,micro-mirror array 1, modulates the direction of reflected light (6 and7) so as to define a predetermined light image 8 projected onto the chipor wafer 4. The direction of the reflected light alters the lightintensity transmitted from each pixel to each feature. In essence, thespatial light modulator operates as a directional and intensitymodulator.

The micro-mirror array 1 can be provided by, for example, themicro-mirror array of the Texas Instruments (TI) DMD, in particular, theTI “SVGA DLP™” subsystem. The Texas Instruments “SVGA DLP™” subsystemwith optics may be modified for use in the present invention. The TexasInstruments “SVGA DLP™” subsystem includes a micro-mirror array (shownas micro-mirror array 1 in FIG. 1), a light source, a color filterwheel, a projection lens, and electronics for driving the array andinterfacing to a computer. The color filter wheel is replaced with abandpass filter having, for example, a bandpass wavelength of 365-410 nm(wavelength dependent upon the type of photochemicals selected for usedin the process). For additional brightness at wavelengths of, forexample, 400-410 nm, the light source can be replaced with arc lamp 3and appropriate homogenizing and collimating optics. The lens includedwith the device is intended for use at very large conjugate ratios andis replaced with lens 2 or set of lenses appropriate for imaging themicro-mirror array 1 onto chip or wafer 4 with the desiredmagnification. Selection of the appropriate lens and bandpass filter isdependent on, among other things, the requisite image size to be formedon the chip, the type of spatial light modulator, the type of lightsource, and the type of photoresist and photochemicals being used in thesystem and process.

A symmetric lens system (e.g., lenses arranged by type A-B-C-C-B-A) usedat 1:1 magnification (object size is the same as the image size) isdesirable because certain aberrations (distortion, lateral color, coma)are minimized by symmetry. Further, a symmetric lens system results in arelatively simple lens design because there are only half as manyvariables as in an asymmetric system having the same number of surfaces.However, at 1:1 magnification the likely maximum possible chip size is10.88 mm×8.16 mm with a VGA device, or 10.2 mm×13.6 mm with an SVGAdevice. Synthesis of, for example, a standard GeneChip® 12.8 mm×12.8 mmchip uses an asymmetric optical system (e.g., a magnification of about1.25:1 with SVGA device) or a larger micro-mirror array (e.g. 1028×768mirrors) if the mirror size is constant. In essence, the lensmagnification can be greater than or less than 1 depending on thedesired size of the chip.

In certain applications of the invention, a relatively simple lenssystem, such as a back-to-back pair of achromats or camera lens, isadequate. A particularly useful lens for some applications of theinvention is the Rodenstock (Rockford, Ill.) Apo-Rodagon D. This lens isoptimized for 1:1 imaging and gives good performance at magnificationsup to about 1.3:1. Similar lenses may be available from othermanufacturers. With such lenses, either the Airy disk diameter or theblur circle diameter will be rather large (maybe 10 um or larger). SeeModern Optical Engineering, 2d Edition, Smith, W. J., ed., McGraw-Hill,Inc., New York (1990). For higher-quality synthesis, the feature size isseveral times larger than the Airy disk or blur circle. Therefore, acustom-made lens with resolution of about 1-2 um over a 12.8 mm×12.8 mmfield is particularly desirable.

A preferred embodiment of synthesizing polymer arrays with aprogrammable micro-mirror array using the DMT process with photoresisttakes place as follows. First, a computer file is generated andspecifies, for each photolithography step, which mirrors in themicro-mirror array 1 need to be on and which need to be off to generatea particular predetermined image pattern. Next, the individual chip orthe wafer from which it is made 4 is coated with photoresist on thesynthesis surface and is mounted in a holder or flow cell (not shown) onthe photolithography apparatus so that the synthesis surface is in theplane where the image of the micro-mirror array 1 will be formed. Thephotoresist may be either positive or negative thus allowingdeprotection at locations exposed to the light or deprotection atlocations not exposed to the light, respectively (example photoresistsinclude: negative tone SU-8 epoxy resin (Shell Chemical) and those shownin the above cited patents and U.S. patent application Ser. No.08/634,053). A mechanism for aligning and focusing the chip or wafer isprovided, such as a x-y translation stage. Then, the micro-mirror array1 is programmed for the appropriate configuration according to thedesired predetermined image pattern, a shutter in the arc lamp 3 isopened, the chip or wafer 4 is illuminated for the desired amount oftime, and the shutter is closed. If a wafer (rather than a chip) isbeing synthesized; a stepping-motor-driven translation stage moves thewafer by a distance equal to the desired center-to-center distancebetween chips and the shutter of the arc lamp 3 is opened and closedagain, these two steps being repeated until each chip of the wafer hasbeen exposed.

Next, the photoresist is developed and etched. Exposure of the wafer 4to acid then cleaves the DMT protecting groups from regions of the waferwhere the photoresist has been removed. The remaining photoresist isthen stripped. Then DMT-protected nucleotides containing the desiredbase (adenine (A), cytosine (C), guanine (G), or thymine (T)) arecoupled to the deprotected oligonucleotides.

Subsequently, the chip or wafer 4 is re-coated with photoresist. Thesteps from mounting the photoresist coated chip or wafer 4 in a holderthrough re-coating the chip or wafer 4 with photoresist are repeateduntil the polymer array synthesis is complete.

It is worth noting that if a DPD method, using for example1-(6-nitro-1,3-benzodioxol-5-yl)ethyloxycarbonyl (MeNPOC) chemistry, ora PAG method, using a polymer film containing a photoacid generator(PAG), are used for polymer array synthesis then photoresist would notbe used and the process is somewhat simplified. However, the use of adirect write optical Lithography system with a spatial light modulatoris also applicable to performing a process of deprotection of reactionsites using the DPD and PAG methods without photoresist.

As is clear from the above described method for polymer array synthesis,no photomasks are needed. This simplifies the process by eliminatingprocessing time associated with changing masks in the opticallithography system and reduces the manufacturing cost for polymer arraysynthesis by eliminating the cost of the masks as well as processingdefects associated with using masks. In addition, the process hasimproved flexibility because reprogramming the optical lithographysystem to produce a different generate and verify new photomasks, thusmaking it possible to transfer an image pattern computer file directlyfrom a CAD or similar system to the optical lithography system orproviding electronic signals directly from the CAD system to drive theoptical lithography system's means for dynamically producing the desiredlight pattern (e.g., spatial light modulator). Therefore, the opticallithography system is simplified and more efficient than conventionalphotomask based optical lithography systems. This is particularlyvaluable in complex multiple step photolithography processing; forexample polymer array synthesis of GeneChip® probe arrays having upwardsof seventy or more cycles, especially when many different products aremade and revised

As indicated above, substrates coated with photoresist are employed inpreferred embodiments of the invention, e.g., using the DMT process withphotoresist. The use of photoresist with photolithographic methods forfabricating polymer arrays is discussed in McGall et al., Chemtech, pp.22-32 (February 1997); McGall et al., Proc. Natl. Acad. Sci., U.S.A.,Vol. 93, pp. 13555-13560 (November 1996) and various patents citedabove, all of which are incorporated by reference in their entireties.Alternatively, polymer array synthesis processing can be performed usingphotoacid generators without using a conventional photoresist, e.g.using the PAG process, or using direct photodeprotection without usingany photoresist, e.g., using the DPD process. The use of photoacidgenerators is taught in U.S. application Ser. No. 08/969,227, filed Nov.13, 1997. However, the present invention is particularly useful whenusing the DMT and PAG processes for polymer array synthesis.

When synthesizing nucleic acid arrays, the photochemical processes usedto fabricate the arrays is preferably activated with light having awavelength greater than 365 nm to avoid photochemical degradation of thepolynucleotides used to create the polymer arrays. Other wavelengths maybe desirable for other probes. Many photoacid generators (PAGs) based ono-nitrobenzyl chemistry are useful at 365 nm. Further, when using themirror array from Texas Instruments discussed above, the PAG ispreferably sensitive above 400 nm to avoid damage to the mirror array.To achieve this, p-nitrobenzyl esters can be used in conjunction with aphotosensitizer. For example, p-nitrobenzyltosylate and2-ethyl-9,10-dimethoxy-anthracene can be used to photochemicallygenerate toluenesulfonic acid at 405 nm. See S. C. Busman and J. E.Trend, J. Imag. Technol., 1985, 11, 191; A. Nishida, T. Hamada, and O.Yonemitsu, J. Org. Chem., 1988, 53, 3386. In this system, the sensitizerabsorbs the light and then transfers the energy to thep-nitrobenzyltosylate, causing dissociation and the subsequent releaseof toluensulfonic acid. Alternate sensitizers, such as pyrene,N,N-dimethylnapthylamine, perylene, phenothiazine, canthone,thiocanthone, actophenone, and benzophenone that absorb light at otherwavelengths are also useful.

A variety of photoresists sensitive to 436-nm light are available foruse in polymer array synthesis and will avoid photochemical degradationof the polynucleotides.

A second preferred mechanical modulator that may be used in theinvention is the Grating Light Valve™ (GLV™) available from SiliconLightMachines, Sunnyvale, Calif., USA. The GLV™ relies on micromachinedpixels that can be programmed to be either reflective or diffractive(Grating Light Valve™ technology). Information regarding certain of themechanical modulators discussed herein is obtained at http://www.ti.com(Texas instruments) and http://siliconlight.com. (SiliconLightMachines).

Although preferred spatial light modulators include the mechanicalmodulators DMD™ available from Texas Instruments and the GLV™ availablefrom Silicon LightMachines, various types of spatial light modulatorsexist and may be used in the practice of the present invention. SeeElectronic Engineers' Handbook, 3^(rd) Ed., Fink, D. G. andChristiansen, D. Eds., McGraw-Hill Book Co., New York (1989). Deformablemembrane mirror-arrays are available from Optron Systems Inc. (Bedford,Mass.). Liquid-crystal spatial light modulators are available fromHamamatsu (Bridgewater, N.J.), Spatialight (Novato, Calif.), and othercompanies. However, one skilled in the art must be careful to select theproper light source and processing chemistries to ensure that theliquid-crystal spatial light modulator is not damaged since thesedevices may be susceptible to damage by various ultraviolet (UV) light.Liquid-crystal displays (LCD; e.g., in calculators and notebookcomputers) are also spatial light modulators useful for photolithographyparticularly to synthesize large features. However, reduction opticswould be required to synthesize smaller features using LCDs.

Some spatial light modulators may be better suited than the TexasInstruments device for use with UV light and would therefore becompatible with a wider range of photoresist chemistries. One skilled inthe art will choose the spatial modulator that is compatible with thechosen wavelength of illumination and synthesis chemistries employed.For example, the device from Texas Instruments DMD™ should not be usedwith UV illumination because its micro-mirror array may be damaged by UVlight. However, if the passivation layer of the micro-mirror array ismodified or removed, the Texas Instruments DMD™ could be used in theinvention with UV light.

One embodiment that is particularly useful when extremely highresolution is required involves imaging the micro-mirror array using asystem of the type shown in FIG. 2. In this system, a lens 12 images themicro-mirror array 11 (e.g., DMD™ or GLV™) onto an array 10 having anarray of micro-lenses 15 or non-imaging light concentrators. Eachelement of the array 10 focuses light onto the chip or wafer, e.g., GeneChip array 14. Each micro-lens 15 produces an image of one pixel of themicro-mirror array 11. Optics 16, including a shaping lens 17 may beincluded to translate light from a light source 13 onto the micro-mirrorarray 11.

For example, if an SVGA DLP™ device is imaged with 1:1 magnificationonto a micro-lens array 10, an appropriate micro-lens array 10 canconsist of 800×600 lenses (micro-lenses 15) with 17 μm center-to-centerspacing. Alternatively, the micro-lens array can consist of 400×300 17μm diameter lenses with 34 μm center-to-center spacing, and with opaquematerial (e.g., chrome) between micro-lenses 15. One advantage of thisalternative is that cross-talk between pixels is reduced. The lightincident upon each micro lens 15 can be focused to a spot size of 1-2μm. Because the spot size is much less than the spacing betweenmicro-lenses, a 2-axis translation stage (having, in these examples, arange of travel of at least either 17 μm×17 μm or 34 μm×34 μm) isnecessary if complete coverage of the chip or wafer 14 is desired.

Micro-lenses 15 can be diffractive, refractive, or hybrid (diffractiveand refractive). Refractive micro-lenses can be conventional orgradient-index. A portion of a diffractive micro-lens array 10 is shownin FIG. 3 and has individual micro-lenses formed as circles commonlyknown as Fresnel Zone Plates 20. Alternatively an array of non-imaginglight concentrators can be employed. An example of such an approachwould include a short piece of optical fiber which may be tapered to asmall tip.

Furthermore, some spatial light modulators are designed to modulatetransmitted rather than reflected light. An example of a transmissivespatial light modulator is a liquid crystal display (LCD) and isillustrated in another embodiment, shown in FIG. 4. This embodimentincludes a light source 33 providing light 35, transmissive spatiallight modulator 31 and a computer 39 providing electronic controlsignals to the transmissive spatial light modulator 31 through cables 40so as to transmit a desired light image 38 on the chip or wafer 34. Thecomputer 39 may be, for example, a unique programmable controller, apersonal computer (PC), or a CAD system used to design the desired imagepattern.

Using a transmissive spatial light modulator has even additionaladvantages over the conventional optical lithography system. Reflectivespatial light modulators require a large working distance between themodulator and the lens so that the lens does not block the incidentlight. Designing a high performance lens with a large working distanceis more difficult than designing a lens of equivalent performance withno constraints on the working distance. With a transmissive spatiallight modulator the working distance does not have to be long and lensdesign is therefore easier. In fact, as show in FIG. 4, sometransmissive spatial light modulators 31 might be useful for proximityor contact printing with no lens at all, by locating the modulator veryclose to the chip or wafer 34.

In fact, the transmissive spatial light modulator in the embodiment ofFIG. 4 could be replaced by an LED array or a semiconductor laser arraysemitting light of the appropriate wavelength, each of which not only maybe operated to dynamically define a desired image but also act as thelight source. Thus, as modified, this embodiment would be simplified soas to not require a separate light source.

Although discussed herein in reference to polymer array synthesis, oneskilled in the art will appreciate that the present invention has avariety of applications including, among others, silicon micromachiningand custom semiconductor chip manufacturing. However, use of some typesof spatial light modulators with the invention may result in limitingthe types of geometries available in silicon micromachining and customsemiconductor chip manufacturing applications. It is understood that theexamples and embodiments described herein are for illustrative purposesonly and that various modifications or changes in light thereof will besuggested to persons skilled in the art and are to be included withinthe spirit and purview of this application and scope of the appendedclaims.

All publications, patents, and patent applications cited herein arehereby incorporated by reference in their entirety for all purposes.Application Ser. No. 08/426,202 (filed Apr. 21, 1995) relates to thepresent invention and is hereby incorporated by reference for allpurposes.

1. A method for deprotecting reaction sites on a substrate comprisingthe steps of: providing a substrate having protected reaction sites;modulating light direction with a spatial light modulator so as togenerate a predetermined light pattern used for deprotecting selectedportions of said protected reaction sites. 2-36. (canceled)
 37. Anapparatus for constructing DNA probes comprising: (a) a reactorproviding a reaction site at which nucleotide addition reactions may beconducted; (b) a light source providing a light capable of promotingnucleotide addition reactions; (c) a set of electronically addressablemicromirrors positioned along an optical path between the light sourceand the reactor to receive and reflect the light, the micromirrorsseparated by lanes having lane widths; and (d) projection opticspositioned along the optical path between the reaction site and theimage generator to focus an image of the lanes on the reaction site;wherein the resolution of the projection optics expressed as aseparation distance between resolvable line pairs is greater than halfthe lane width.
 38. The apparatus of claim 37 wherein the resolutionexpressed as a separation distance between resolvable line pairs isgreater than the lane width.
 39. The apparatus of claim 37 wherein theresolution expressed as a separation distance between resolvable linepairs is greater than twice the lane width.
 40. The apparatus of claim37 wherein the resolution is calculated according to the formula:LW=kλ/NA where: k is within a range of 0.7 to 0.5, λ is the wavelengthof the light, and NA is the numeric aperture of the projection optics.41. The apparatus of claim 40 wherein NA is measured as the sine of thehalf angle of a cone of light received from the projection optics by acentral point of the reactor.
 42. The apparatus of claim 40 wherein thenumeric aperture is approximated by the aperture of a final element ofthe projection optics divided by twice a focal length of that finalelement.
 43. The apparatus of claim 37 wherein the reactor is a flowcell having one or more reaction chambers in which nucleotide additionreactions may be conducted.
 44. The apparatus of claim 43 wherein theflow cell further comprises a housing composed of a lower base, an uppercover section and a gasket mounted on the base, wherein a transparentsubstrate is secured between the upper cover section and the base todefine a sealed reaction chamber between the substrate and the base thatis sealed by the gasket, and wherein at least one channel extendsthrough the housing from an input port to the reaction chamber and fromthe reaction chamber to an output port, wherein the active surface ofthe substrate faces the sealed reaction chamber.
 45. The apparatus ofclaim 43 wherein the flow cell contains a plurality of reaction chambersin which nucleotide addition reactions may be conducted in solutionphase.
 46. The apparatus of claim 43 wherein the flow cell comprises acell member having an upper surface and a lower surface and defining aplurality of channels permitting fluid communication between said uppersurface and lower surface, said channels defining a plurality ofreaction chambers in which nucleotide addition reactions can beconducted in solution phase.
 47. The apparatus of claim 37 wherein theprojection optics include focusing lenses and an adjustable iris,wherein one of the lenses passes light through the adjustable iris andthe other lens receives the light passed through the iris and focusesthat light into the reactor.
 48. The apparatus of claim 37 wherein theprojection optics include a concave mirror and a convex mirror, theconcave mirror reflecting light from the electronically addressablemicromirrors to the convex mirror which reflects it back to the concavemirror which reflects the light into the flow cell where it is imaged.49. The apparatus of claim 37 wherein the projection optics form anOffner optical system.
 50. The apparatus of claim 37 wherein theprojection optics are telecentric.
 51. The apparatus of claim 37 furthercomprising a filter receiving the light from the light source and whichselectively passes only desired wavelengths through to the set ofelectronically addressable micromirrors.
 52. The apparatus of claim 37further comprising a computer connected to the set of electronicallyaddressable micromirrors to provide command signals to control thepositioning of the micromirrors to provide a desired pattern forprojection into the reactor.
 53. The apparatus of claim 37 wherein thelight is in the range of ultraviolet to near ultraviolet wavelengths.54. The apparatus of claim 37 wherein the image of the lanes issubstantially the same size as the lanes in the electronicallyaddressable micromirrors array.
 55. The apparatus of claim 37 furthercomprising a DNA synthesizer connected to supply reagents to thereactor.
 56. The apparatus of claim 37 wherein the lanes are gapsbetween adjacent electronically addressable micromirrors.
 57. Theapparatus of claim 56 wherein the resolution expressed as a separationdistance between resolvable line pairs is greater than one micrometer.58. The apparatus of claim 56 wherein the resolution expressed as aseparation distance between resolvable line pairs is greater than twomicrometers.
 59. The apparatus of claim 37 wherein the lanes areelectronically addressable micromirrors receiving a fixed signal todirect light away from the projection optics.
 60. The apparatus of claim37 wherein the projection optics provides a magnification substantiallyof one.